Objectives We assessed the association between depression and sudden cardiac death (SCD) and cardiac events among individuals without baseline coronary heart disease (CHD). Background Depression is a risk factor for cardiac events and mortality among those with CHD, possibly from arrhythmia. Methods We studied depressive symptoms, and a proxy variable for clinical depression consisting of severe symptoms and/or antidepressant medication use, and their relationship to cardiac events in the Nurses’ Health Study. Questionnaires in 1992, 1996, and 2000 assessed symptoms with the Mental Health Index (MHI-5), and antidepressant use was assessed in 1996 and 2000. Primary endpoints included SCD, fatal CHD, and non-fatal myocardial infarction (MI). Results Among 63,469 women without prior CHD/stroke in 1992, 7.9% had MHI-5 scores (<53) previously found to predict clinical depression. Depressive symptoms were associated with CHD events, and the relationship was strongest for fatal CHD, where the association remained significant even after controlling for CHD risk factors (HR=1.49; 95% CI 1.11–2.00 for MHI-5 score<53). In models from 1996 onward, our proxy variable for clinical depression was most associated with SCD in multivariable models (HR=2.33, 95% CI 1.47–3.70), and this risk was primarily due to a specific relationship between antidepressant use and SCD (HR=3.34, 95% CI 2.03–5.50). Conclusions In this cohort of women without baseline CHD, depressive symptoms were associated with fatal CHD, and a measure of clinical depression including antidepressant use was specifically associated with SCD. Although antidepressant use may be a marker of worse depression, its specific association with SCD merits further study. CONDENSED ABSTRACT We prospectively analyzed the association between depression and cardiac events in the Nurses’ Health Study. Symptoms of depression as measured by Mental Health Index (MHI-5) score were directly associated with risk of CHD events, and the relationship was strongest for fatal CHD. A proxy variable for clinical depression comprised of MHI-5 score<53 or antidepressant use was strongly associated with sudden cardiac death (SCD), primarily due to a specific relationship between antidepressant use and SCD. Although antidepressant use may be a marker of worse depression, its specific association with SCD merits further study.

In this large, population-based study, increased positive affect was protective against 10-year incident CHD, suggesting that preventive strategies may be enhanced not only by reducing depressive symptoms but also by increasing positive affect.

Background-␣-Linolenic acid, an intermediate-chain n-3 fatty acid found primarily in plants, may decrease the risk of fatal coronary heart disease (CHD) through a reduction in fatal ventricular arrhythmias and sudden cardiac death (SCD). Methods and Results-We prospectively examined the association between dietary intake of ␣-linolenic acid assessed via updated food-frequency questionnaires and the risk of SCD, other fatal CHD, and nonfatal myocardial infarction (MI) among 76 763 women participating in the Nurses' Health Study who were free from cancer and completed a dietary questionnaire at baseline in 1984. During 18 years of follow-up, we identified 206 SCDs, 641 other CHD deaths, and 1604 nonfatal MIs. After controlling for coronary risk factors and other fatty acids, including long-chain n-3 fatty acids, the intake of ␣-linolenic acid was inversely associated with the risk of SCD (P for trend, 0.02) but not with the risk of other fatal CHD or nonfatal MI. Compared with women in the lowest quintile of ␣-linolenic acid intake, those in the highest 2 quintiles had a 38% to 40% lower SCD risk. This inverse relation with SCD risk was linear and remained significant even among women with high intakes of long-chain n-3 fatty acids. Conclusions-These prospective data suggest that increasing dietary intake of ␣-linolenic acid may reduce the risk of SCD but not other types of fatal CHD or nonfatal MI in women. The specificity of the association between ␣-linolenic acid and SCD supports the hypothesis that these n-3 fatty acids may have antiarrhythmic properties. (Circulation. 2005;112: 3232-3238.)

More severe symptoms of depression predict shocks for VT/VF among ICD patients. The elevated risk of VT/VF among patients with CAD and depression suggests that arrhythmia may contribute significantly to total mortality in this subgroup.